Samples of Carpesium genus used as traditional remedies for the treatment of parasite infections were collected, and methanol extracts were obtained by sonication. The ethylacetate-, n-butanol- and H(2)O-soluble fractions exhibited weak antiplasmodial activity (IC(50)>> 100 microg/ml; IC(50), 50% inhibitory concentration). However, the chloroform fraction exhibited more impressive antiplasmodial activity (IC(50) = 8.2 microg/ml). The antiplasmodial activity of the chloroform fractions was evaluated in vitro against the chloroquine-resistant D10 strain of Plasmodium falciparum. Bioactivity-guided isolation of the chloroform fractions of the whole plants of Carpesium rosulatum has led to the isolation of a sesquiterpene lactone, ineupatorolides A, displaying high antiplasmodial activity (IC(50) = 0.007 microg/ml). This is the first report of the isolation of ineupatorolides A from this species and of its remarkable antiplasmodial activity.